A bioprinted human-glioblastoma-on-a-chip for the identification of patient-specific responses to chemoradiotherapy.
Hee-Gyeong YiYoung Hun JeongYona KimYeong-Jin ChoiHyo Eun MoonHye-Kyung ParkKyung Shin KangMihyeon BaeJinah JangHyewon YounSun Ha PaekDong Woo ChoPublished in: Nature biomedical engineering (2019)
Patient-specific ex vivo models of human tumours that recapitulate the pathological characteristics and complex ecology of native tumours could help determine the most appropriate cancer treatment for individual patients. Here, we show that bioprinted reconstituted glioblastoma tumours consisting of patient-derived tumour cells, vascular endothelial cells and decellularized extracellular matrix from brain tissue in a compartmentalized cancer-stroma concentric-ring structure that sustains a radial oxygen gradient, recapitulate the structural, biochemical and biophysical properties of the native tumours. We also show that the glioblastoma-on-a-chip reproduces clinically observed patient-specific resistances to treatment with concurrent chemoradiation and temozolomide, and that the model can be used to determine drug combinations associated with superior tumour killing. The patient-specific tumour-on-a-chip model might be useful for the identification of effective treatments for glioblastoma patients resistant to the standard first-line treatment.
Keyphrases
- endothelial cells
- extracellular matrix
- end stage renal disease
- newly diagnosed
- ejection fraction
- high throughput
- prognostic factors
- chronic kidney disease
- rectal cancer
- locally advanced
- squamous cell carcinoma
- circulating tumor cells
- high glucose
- patient reported outcomes
- white matter
- high density
- ultrasound guided
- squamous cell
- papillary thyroid
- pluripotent stem cells
- smoking cessation
- cerebral ischemia